title: Effect of two pyrimidine analogs on accumulation of tubulin in NHIK 3025 cells.
abstract: Accumulation of tubulin as compared with the accumulation of total cellular protein in human NHIK 3025 cells treated with the sulfone 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137) and the sulfoxide 2-(2-thenyl)sulfinyl-5-bromopyrimidine (NY 4138), two mitotic inhibitors, were investigated by two-parametric flow cytometry. Following a 4 h treatment with NY 4137 tubulin accumulation is inhibited while total protein continues to accumulate. After treatment for 4 h with NY 4138 the accumulation of total protein is approximately constant, while the accumulation of tubulin is reduced although not to the same degree as that found for NY 4137-treated cells. In addition, the percentage tubulin SH-groups (6.89 +/- 0.14) remaining after treatment of purified rat brain tubulin with NY 4137 or NY 4138 was determined. Treatment with 0.0125 mM NY 4137 reduced the number of tubulin SH-groups detectable with dithiobis benzoate or from 6.89 +/- 0.14 before treatment to about 4 after treatment. However, practically all SH-groups of tubulin remain detectable following treatment with the same concentration of NY 4138. From the results described in this report we infer that NY 4137 binds to tubulin SH-groups and that inhibition of tubulin accumulation follows as a secondary effect.
authors.affiliation: Department of Tissue Culture, Norwegian Radium Hospital, Montebello, Oslo.
authors.forename: M E
authors.initials: ME
authors.lastname: Juul
authors.forename: J M
authors.initials: JM
authors.lastname: Dornish
authors.forename: N O
authors.initials: NO
authors.lastname: Juul
authors.forename: E O
authors.initials: EO
authors.lastname: Pettersen
authors.forename: R
authors.initials: R
authors.lastname: Oftebro
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002460:Cell Line; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D014404:Tubulin / Q000378:metabolism*
chemical_list: D011743:Pyrimidines; D014404:Tubulin; C047250:NY 4138; C051723:2-(2-thenyl)sulfonyl-5-bromopyrimidine